Now that a reasonable amount of information is known of the lysosome and its complement of acid hydrolases in skeletal muscle, we would like to study the involvement of the lysosome in the progressive degeneration of muscle in vitamin E-deficiency. Muscle tissue of the vitamin E-deficient guinea pigs will be studied at 15 days (early biochemical changes); 21 days (first observable morphological changes with light microscope); and 30 days (gross clinical symptoms). The lysosome populations and enzymes will be characterized by free activity studies, differential centrifugation, and rate and isopycnic zonal centrifugation. The formation of lipofuscin granules will be followed, and the possible involvement of catalase-containing particles (peroxisomes?) in the denaturation of protein and initiation of autophagy will be examined. Tissue sections will be studied by electron microscopy at the three stages for further supportive evidence of the lysosome originating from the sarcoplasmic reticulum. The major proteolytic enzyme cathepsin D, and a possible neutral and alkaline protease, will be isolated by preparative and analytical isoelectric focusing, and antisera to cathepsin D will be prepared for studies of immunoinhibition of the enzyme.